Kim Tae Eun, Lee Hack Sup, Lee Yong Beom, Hong Seung Hwan, Lee Young Seek, Ichinose Hiroshi, Kim Seung U, Lee Myung Ae
Brain Disease Research Center, Ajou University School of Medicine, Suwon 442-749, Republic of Korea.
Biochem Biophys Res Commun. 2003 Jun 13;305(4):1040-8. doi: 10.1016/s0006-291x(03)00879-9.
Neural stem cells are self-renewing cells capable of differentiating into all neural lineage cells in vivo and in vitro. In the present study, coordinated induction of midbrain dopaminergic phenotypes in an immortalized multipotent neural stem cell line can be achieved by both overexpression of nuclear receptor Nurr1, and fibroblast growth factor-8 (FGF-8), and sonic hedgehog (Shh) signals. Nurr1 overexpression induces neuronal differentiation and confers competence to respond to extrinsic signals such as Shh and FGF-8 that induce dopaminergic fate in a mouse neural stem cell line. Our findings suggest that immortalized NSCs can serve as an excellent model for understanding mechanisms that regulate specification of ventral midbrain DA neurons and as an unlimited source of DA progenitors for treating Parkinson disease patients by cell replacement.
神经干细胞是能够在体内和体外分化为所有神经谱系细胞的自我更新细胞。在本研究中，通过过表达核受体Nurr1、成纤维细胞生长因子8（FGF-8）和音猬因子（Shh）信号，可以在永生化多能神经干细胞系中实现中脑多巴胺能表型的协同诱导。Nurr1的过表达诱导神经元分化，并赋予细胞对诸如Shh和FGF-8等外在信号作出反应的能力，这些信号在小鼠神经干细胞系中诱导多巴胺能命运。我们的研究结果表明，永生化神经干细胞可以作为一个优秀的模型，用于理解调节腹侧中脑多巴胺能神经元特化的机制，并作为多巴胺能祖细胞的无限来源，通过细胞替代疗法治疗帕金森病患者。
